DREADDs

Designer Receptors Exculsively Activated by Designer Drugs

DREADDs are novel pharmacogenetic tools for turning neurons on and off in a controlled manner. Through a process of evolutionary mutagenesis, human muscarinic receptors were found to have point mutations in their genetic code that cause them to lose their ability to bind their natural ligand, acetylcholine. Instead, they preferentially bind the synthetic ligand Clozapine-N-Oxide (CNO). There are two main variants of the DREADDs: 1) the Gq-DREADD which causes neuronal activation, and 2) the Gi-DREADD that causes neuronal deactivation.

DREADDs were developed by our collaborator, Dr. Bryan Roth at UNC--Chapel Hill.

One limitation of this treatment approach is the requirement for an initial neurosurgery to infuse the virus into the brain area of interest. Thereafter, however, a systemic dosing of CNO can be used to activate or deactivate neurons in that brain region. This pharmacogenetic treatment approach is thus an attractive candidate for clinical therapies.